Genomic ancestry as a risk factor for diabetic retinopathy in patients with type 1 diabetes from an admixed population: a nested case-control study in Brazil.

AIMS: The influence of genetic factors on the development and progression of diabetic retinopathy is still unclear. Previous studies showed controversial results. We aimed to characterize the relationship between genomic ancestry and self-reported color/race with severe diabetic retinopathy in patients with type 1 diabetes belonging to a highly admixed population. METHODS: This study was a nested case-control based on data collected from a large cross-sectional, nationwide survey conducted in clinics from all five geographic regions of Brazil. For the present study, we included 414 individuals. Cases (n = 176) were considered if they had severe non-proliferative or proliferative diabetic retinopathy, and controls (n = 238) were type 1 diabetes patients without retinopathy, matched for diabetes duration by a range of 5 years. Indirect ophthalmoscopy was performed, and individual genomic ancestry was inferred using a panel of 46 ancestry informative markers. RESULTS: The backward stepwise logistic regression analysis showed that African genomic ancestry (OR 3.9, p = 0.045), HbA1c (OR 1.24, p = 0.001), glomerular filtration rate (OR 0.98, p < 0.001) and hypertension (OR 2.52, p < 0.001) were associated with severe diabetic retinopathy after adjusting for clinical and demographic data. Self-reported color/race was not statistically associated with diabetic retinopathy. CONCLUSIONS: Genomic ancestry, as well as clinical variables such as hypertension, impaired glomerular filtration rate and poor diabetes control (HbA1c), was important risk factor for the development of severe diabetic retinopathy. Further studies are needed, especially in highly admixed populations, to better understand the role of genomic ancestry and possible genes that might be associated with the development and/or progression of diabetic retinopathy.

Diabetic Retinopathy May Indicate an Increased Risk of Cardiovascular Disease in Patients With Type 1 Diabetes-A Nested Case-Control Study in Brazil.

Objective: Cardiovascular disease, the leading cause of death worldwide, and diabetic retinopathy, the main cause of blindness in economically active populations, share clinical risk factors, and pathophysiological features. The aim of this study is to examine the association between diabetic retinopathy, cardiovascular disease, and common risk factors in patients with type 1 diabetes. Design and Methods: This nested case-control study was performed in patients from the Brazilian Type 1 Diabetes Study Group, a nationwide survey that was conducted in Brazil and enrolled 1,760 patients with type 1 diabetes. A total of 342 patients were selected (57 cases with macrovascular disease and 285 controls who were matched for duration of diabetes and gender). Results: In the exploratory analysis, stratified by cardiovascular disease, the following variables were statistically significant: age (p=0.037), hypertension (p=0.035), high BMI (p = 0.046), diabetic retinopathy (p = 0.003), and chronic kidney disease (p = 0.026). By multivariate logistic regression, patients with diabetic retinopathy were more likely to develop cardiovascular disease (OR 2.16, 95% CI 1.16-4.02, p = 0.015). Although to a lesser extent than diabetic retinopathy, higher BMI levels were also related to an increase in the risk of cardiovascular disease of 1.08 (95% CI 1.01-1.15, p = 0.024). Conclusion: The presence of diabetic retinopathy indicates a greater risk for cardiovascular disease in Brazilian patients with type 1 diabetes. Further studies are warranted to determine whether a noninvasive exam, such as fundoscopy, could help identify patients who show an increased risk for cardiovascular disease.

Current epidemiology of diabetic retinopathy in patients with type 1 diabetes: a national multicenter study in Brazil.

BACKGROUND: Diabetic retinopathy is the leading cause of blindness in economically active populations. The aims of this study were to estimate the prevalence and to identify risk factors for diabetic retinopathy in patients with type 1 diabetes in Brazil. METHODS: This was a nationwide, cross-sectional study conducted between August 2010 and August 2014. The study included 1760 patients with type 1 diabetes. Patients underwent a standard questionnaire, clinical and laboratory analyses and were screened for diabetic retinopathy. To analyze the risk factors related to diabetic retinopathy, two models of logistic regression models were performed, one considering vision-threatening cases and the other with any diabetic retinopathy cases as dependent variables. The group with vision-threatening included patients with severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and macular edema. RESULTS: In total, 1644 patients (mean age, 30.1± 12.0 years; duration of diabetes, 15.3 ± 9.3 years; female, 55.8%) were studied. 35.7% presented diabetic retinopathy and 12% presented vision-threatening diabetic retinopathy. Three risk factors associated with diabetic retinopathy were in common to both groups: longer diabetes duration (OR 1.07; 95% CI, 1.05-1.09), higher levels of HbA1c (OR 1.24; CI, 1.17-1.32) and higher levels of serum uric acid (OR 1.22; CI, 1.13-1.31) (p < 0.001 for all comparisons). CONCLUSION: The higher rate of vision-threatening retinopathy found in our study highlights the need to improve access to eye care and screening programs for diabetic retinopathy in Brazil. In addition to traditional risk factors, we found an association between serum uric acid levels and diabetic retinopathy. Further studies are needed to address this association.